methyl 3-amino-4-(3,4-dimethoxyphenyl)-2-thiophene carboxylate | 539821-21-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-amino-4-(3,4-dimethoxyphenyl)-2-thiophene carboxylate
• 英文别名: Methyl 3-amino-4-(3,4-dimethoxyphenyl)thiophene-2-carboxylate
• CAS: 539821-21-1
• 化学式: C₁₄H₁₅NO₄S
• 分子量: 293.343
• InChiKey: CDWOSWSEVQAOSP-UHFFFAOYSA-N

物化性质

• 熔点：
  154 °C
• 沸点：
  427.6±45.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-4-(3,4-dimethoxyphenyl)-2-thiophene carboxylate 在 4-氯吡啶盐酸盐 、 三溴化硼 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 9.25h， 生成 3-(3,4-dihydroxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z
• 作为产物：
  描述：

  3,4-二甲氧基苯乙腈 在 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl 3-amino-4-(3,4-dimethoxyphenyl)-2-thiophene carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel Thienopyrrolizinones as Antitubulin Agents

  摘要：

  Herein, we describe the structure-activity relationship study of a new 3-aryl-8H-thieno[2,3-b]pyrrolizin-8-one series of antitubulin agents. The pharmacological results from the National Cancer Institute in vitro human disease oriented tumor cell line screening allowed us to identify compound 1d (NSC 676693) as a very efficient antitumoral drug in all cancer cell lines tested. This prompted us to define the structural requirements essential for this antiproliferative activity. Among all analogues synthesized in this study, compound 1o was the most promising, being 10-fold more potent than compound 1d. Its activity over a panel of nine tumoral cell lines was in the nanomolar range for all of the histological types tested, and surprisingly, the resistant KB-A1 cell line was also sensitive to this compound. Moreover, a flow cytometric study showed that L1210 cells treated by the most potent compounds were arrested in the G(2)/M phases of the cell cycle with a significant percentage of cells having reinitiated a cycle of DNA synthesis without cell division. This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies that led to a new prodrug chemical approach.

  DOI：

  10.1021/jm030961z

文献信息

• THIENOPYRIMIDINONE DERIVATIVES AS mGluR1 ANTAGONISTS
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20140228565A1

  公开（公告）日：2014-08-14

  Disclosed are thienopyrimidinone derivatives as antagonists that act on metabotropic glutamate receptor subtype 1. The thienopyrimidinone derivatives show pharmacological activity against metabotropic glutamate receptor-related diseases, including pain, such as neuropathic pain and migraine, psychiatric diseases, such as anxiety disorder and schizophrenia, urinary incontinence, and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Also disclosed are methods for preparing the thienopyrimidinone derivatives, and pharmaceutical compositions containing the thienopyrimidinone derivatives as active ingredients.

  披露了作为对代谢型谷氨酸受体亚型1起作用的拮抗剂的噻吩嘧啶酮衍生物。这些噻吩嘧啶酮衍生物显示出对代谢型谷氨酸受体相关疾病的药理活性，包括疼痛，如神经病性疼痛和偏头痛，精神疾病，如焦虑症和精神分裂症，尿失禁，以及神经退行性疾病，如帕金森病和阿尔茨海默病。还披露了制备这些噻吩嘧啶酮衍生物的方法，以及含有这些噻吩嘧啶酮衍生物作为活性成分的药物组合物。
• Synthesis and combinatorial approach of the reactivity of 6- and 7-arylthieno[3,2-d][1,3]oxazine-2,4-diones
  作者：François-Xavier Le Foulon、Emmanuelle Braud、Frédéric Fabis、Jean-Charles Lancelot、Sylvain Rault

  DOI：10.1016/j.tet.2003.10.028

  日期：2003.12

  This paper describes a general procedure for the synthesis of new substituted thiaisatoic anhydrides or 6- or 7-aryl-1H-thiéno[3,2-d][1,3]oxazine-2,4-diones 3a–j and 4a–f. They were synthesized in large scale under microwave heating conditions with high yields. The reactivity vs nucleophilic reagents of these compounds was studied and permitted to develop a simple combinatorial procedure to synthesize

  本文描述了合成新的取代硫代硫杂酸酐或6-或7-芳基-1 H-噻吩并[3,2- d ] [1,3]恶嗪-2,4-二酮3a – j和4a的一般程序。 – f。它们在微波加热条件下以高收率大规模合成。研究了这些化合物的亲核试剂的反应性与亲核试剂的关系，并允许开发一种简单的组合方法来合成新的噻吩脲酸7a – j和8a – j库。
• Thienopyrimidinone derivatives as mGluR1 antagonists
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US09260448B2

  公开（公告）日：2016-02-16

  Disclosed are thienopyrimidinone derivatives as antagonists that act on metabotropic glutamate receptor subtype 1. The thienopyrimidinone derivatives show pharmacological activity against metabotropic glutamate receptor-related diseases, including pain, such as neuropathic pain and migraine, psychiatric diseases, such as anxiety disorder and schizophrenia, urinary incontinence, and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Also disclosed are methods for preparing the thienopyrimidinone derivatives, and pharmaceutical compositions containing the thienopyrimidinone derivatives as active ingredients.

  本发明涉及噻唑嘧啶酮衍生物，作为代谢型谷氨酸受体亚型1的拮抗剂。该噻唑嘧啶酮衍生物对代谢型谷氨酸受体相关疾病具有药理活性，包括疼痛，如神经病性疼痛和偏头痛，精神疾病，如焦虑症和精神分裂症，尿失禁以及神经退行性疾病，如帕金森病和阿尔茨海默病。本发明还涉及制备噻唑嘧啶酮衍生物的方法，以及含有该噻唑嘧啶酮衍生物作为活性成分的药物组合物。
• Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents
  作者：Vincent Lisowski、Cécile Enguehard、Jean-Charles Lancelot、Daniel-Henri Caignard、Stéphanie Lambel、Stéphane Leonce、Alain Pierre、Ghanem Atassi、Pierre Renard、Sylvain Rault

  DOI：10.1016/s0960-894x(01)00403-6

  日期：2001.8

  Structure-activity relationship studies of a new series of tripentones (thieno[2.3-h]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2.3-b]pyrrolizin-8-one 20 (leukemia L1210. IC50= 15 nM) was shown to be a potent inhibitor of tubulin polymerization. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Acid cyclization of amino-substituted heterocycles. Synthesis of 1,3-dioxo- pyrrolo[3,4-c]- and thieno[3,4-c]isoquino- lines and cinnolines
  作者：S. Yu. Zinchenko、R. A. Efimenko、S. Yu. Suikov、K. I. Kobrakov、S. L. Bogza

  DOI：10.1007/s10593-009-0262-2

  日期：2009.3

  The reaction of 3-amino-4-(3,4-dimethoxyphenyl)maleimide and the methyl esters of 3-amino-4-(3,4-dimethoxyphenyl)-5-R-thiophene-2-carboxylic acids with carbonyl compounds and nitrous acid has been investigated. Dioxopyrrolo[3,4-c]- and thieno[3,4-c]isoquinolines and cinnolines were obtained.